The lower vertebrates, amphibia in particular, offer excellent model systems for studying immunity. During the past several years, we have studied various parameters of anti-heterologous erythrocyte responses in three representatives which provide an evolutionary, developmental and functional progression within the Class; the Common American newt, Notophthalmus viridescens (the most-primitive), Xenopus laevis, the South African clawed toad (the intermediate) and the American Grass frog, Rana pipiens (the most advanced). We have been able to describe cellular collaborative events in all three models by using hapten/carrier erythrocyte immunization protocols. We now wish to take advantage of this experience and backlog of information on the phenomenology to begin to deal with questions of causality. There are many phenomena which have been extensively studied in mammalia which are nevertheless, only incompletely understood. Our hope is that by using less complex model systems than ourselves, we can gain increased understanding of such central issues as carrier "effect," the cellular basis of short and long term memory, and different kinds of unresponsiveness. In doing so, we propose to focus on cellular (factor) collaborative events, especially on the regulatory role of thymus-dervied cells using in vivo and in vitro methodologies. Our assay procedures include immunocytoadherence, hemolysin and microtiter hemagglutination.